Axonal loss is an important cause of clinical deficits in patients with MS. Because the etiology of MS is not known, it is impossible to be certain of the precise sequence of events that leads to axonal injury in the disease. The study of another myelin related disorder Pelizaeus- Merzbacher disease (PMD), a disease with a known cause, i.e. mutations affecting the major CNS myelin protein proteolipid protein (PLP1) may provide a better understanding of alternative (to inflammation) disease mechanisms in PMD, which may also be important in MS. Magnetic resonance spectroscopy (MRS), and imaging (MRI), as well as various histological techniques will be utilized to identify the critical domains of this protein that mediate its axon maintaining function in an attempt to better understand the pathogenesis and temporal progression of PMD. Hopefully these findings will provide a model for the clinical deterioration found in PMD as well as MS, and perhaps lead to new therapeutic approaches.